Research Finds Key To Better Memory

New Drugs Helping Brain To Rewire Itself

September 19, 1994|By Ronald Kotulak, Tribune Staff Writer.

The brain encodes the learning, and young brains do it more efficiently than older ones. Out of 50 tone-puff trials, the average young adult in his or her mid-20s automatically will respond 35 times, blinking after the tone and before the puff.

That is pretty successful learning. But people between the ages of 60 and 75, who have leaky doors on their brain cells, will not learn as well. On average they blink only 20 times after 50 tones. Failure to learn means they get more puffs to the eye.

FOR THE RECORD - Additional material published Sept. 24, 1994:Corrections and clarifications.In an article Monday about improving memory, captions explaining magnetic resonance images of a healthy brain and one afflicted with Alzheimer's disease were transposed. The images are part of a study by Leyla Detoledo-Morrell, professor of neurological sciences at Rush-Presbyterian-St. Luke's Medical Center, to identify early changes in the brain caused by Alzheimer's disease.

But when older adults were given nimodipine tablets three times a day for three months, they increased their blinks from 20 to 30, a 50 percent leap in their ability to learn this task over those given placebos instead of nimodipine.

So far nimodipine has had few side effects and the drug already has been approved for treating stroke patients.

While Disterhoft tightens cell doors to improve memory, the University of California's Lynch tinkers with the cell's communications system-its "signal boxes."

Scientists recently discovered a key signal box, called the NMDA receptor, which makes the grand decision to fire an electric charge through the cell, thereby blazing a memory path.

The NMDA signal box sits on the cell surface, awaiting a message from glutamate, a neurotransmitter that races between brain cells like a bicycle messenger yelling, "Pay attention, there's something coming that you might want to learn."

When the glutamate messenger lands on the NMDA receptor, it opens certain doors on the cell surface, letting in energy-carrying sodium particles. These positively charged particles act like batteries to build up the cell's electric charge. When a critical point is reached, a biochemical "spark" is ignited and the cell's connections to other cells are changed-a memory pathway has been forged.

People often block this process with alcohol. Studies show that the reason people can't remember things after heavy drinking is because alcohol molecules clog NMDA receptors. Glutamate messengers bounce off and no signal gets sent.

Knowing how the NMDA receptor works, Lynch and Gary Rogers of the University of California at Santa Barbara devised a chemical that increases the brain's level of attention. The chemical, a member of a family of compounds called ampakines, fits unobtrusively into the receptor.

Normally a glutamate molecule plugs into a receptor, delivers its message, and departs in one-thousandth of a second. But the ampakines, like a wad of gum stuck to the sole of a shoe, make glutamate stick around twice as long.

As a result, the cell doors remain open twice as long and more sodium particles pour in. The NMDA receptor, alerted that something important is happening that should be remembered, fires a charge.

People can do the same thing naturally when they decide to pay greater attention to something they want to learn. Ampakines increase the attention level once they have been aroused, so they make learning easier, Lynch said.

"For the first time we are in the position of being able to say that we designed a drug to hit a specific part of the memory system and that it does improve memory," he said.

Healthy young rats given ampakines learned tasks in half the normal time, he said. No side effects have been noted, and Cortex, a new drug company devoted to developing memory-enhancing agents, plans to start human trials with the ampakines this year, said Lynch, who is a company co-founder.

"We're talking about a pill that you would take, and two minutes later and for the next several hours, information that you're trying to encode in your brain is going to be encoded better," he said.

Can memory enhancers overload the brain with too many memories? Not likely, Lynch said. A neural network model of only 1,000 brain cells, each having a couple hundred connections, was able to learn 10,000 words randomly selected from a dictionary without filling up the system, he said.

"The brain turns out to be a very efficient machine for encoding tons of information," Lynch said. "You'd be amazed at how few connections you need to alter to encode a memory. It's minuscule."

A brain cell fires an electric charge so it can rewire itself as a new memory is formed, and so it can send the new information to other cells.

Northwestern's Aryeh Routtenberg believes he has figured out how those changes are made, at least in a broad sense. In 1984, Routtenberg discovered an important chemical inside cells called PKC, which forms short-term and long-term memory.

Once a cell is alerted to the fact that it needs to form a memory, a second chemical messenger notifies PKC. PKC then runs over to another protein, F1, and pitches a phosphate molecule at it. The phosphate wakes up F1 and it trundles down the branches of the cell to change the synaptic connections.